The physiological role of many serum proteins and the mechanisms of serum transport and cellular uptake of several biological important organic and inorganic ions remain unknown. This lack of information hampers the diagnosis and treatment of several disease states. A serum protein, histidine-rich glycoprotein (HRG), found in human, rat and rabbit sera binds organic ions, like heme, and metal ions, like zinc and copper, with high affinity. This suggests that HRG may have an important role in the transport and tissue disposition of these ions. HRG has been isolated from human serum and its biological and physicochemical properties are under study. Emphasis is placed on the interaction of HRG with heme and with essential metal ions. In a related aspect of study, the levels of HRG in the sera of healthy volunteers and of a variety of patient volunteers will be determined using immunological techniques.